Delhi Institute of Pharmaceutical Sciences and Research, Pushp Vihar, Sector-3, MB Road, New Delhi 110017, India.
Eur J Pharm Sci. 2012 Apr 11;45(5):546-51. doi: 10.1016/j.ejps.2011.11.016. Epub 2011 Dec 3.
The aim of the present study was to evaluate the relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets, using dipeptidyl peptidase-IV (DPP-IV) inhibitor vildagliptin. For measuring pancreatic and islets blood a non-radioactive microsphere technique was used. Vehicle pre-treatment of glucose administered diabetic rats had decrease pancreatic and islets blood flow as compared with glucose administered normal rats. Blood glucose concentrations were not affected after vildagliptin administration in either diabetic or normal rats (10 min after glucose administration). Vildagliptin had no effects on baseline pancreatic or islets blood flow in glucose administered normal rats. Administration of vildagliptin increased both pancreatic and islets blood flow as compared with vehicle treated diabetic rats. Furthermore, diabetic rats showed significant increase in NO and decrease in insulin secretions and vice versa in normal rats. Vildagliptin pre-treatment to both normal and diabetic rats had shown mild decrease in NO, but significantly increased insulin secretions. In addition, vildagliptin itself is able to mobilize intracellular Ca(2+) in pancreatic islets both in absence and presence of glucose. From the present study, we conclude following points (A) administration of vildagliptin augmented the blood flow seen in islets of diabetic rats, (B) islets insulin secretions are independent of islets blood flow and NO, (C) vildagliptin inhibited excessive NO production in diabetic rats that prevents the damage to β-cells due to excessive production of peroxynitrite (ONOO(-)) ions and protects from cytokine-induced suppression of insulin release.
本研究旨在评估二肽基肽酶-4（DPP-4）抑制剂维达列汀对大鼠胰岛血流、一氧化氮、胰岛素和细胞内钙之间关系的影响。采用二肽基肽酶-4（DPP-4）抑制剂维达列汀测量胰岛血流。与给予葡萄糖的正常大鼠相比，给予葡萄糖的糖尿病大鼠的胰岛和胰腺血流在给予 vehicle 预处理后减少。维达列汀给药后，无论是糖尿病大鼠还是正常大鼠的血糖浓度均无变化（葡萄糖给药后 10 分钟）。维达列汀对给予葡萄糖的正常大鼠的基础胰腺或胰岛血流无影响。与 vehicle 处理的糖尿病大鼠相比，维达列汀增加了胰腺和胰岛的血流。此外，糖尿病大鼠的 NO 显著增加，而胰岛素分泌减少，而正常大鼠则相反。维达列汀预处理对正常和糖尿病大鼠的 NO 均有轻度降低，但胰岛素分泌显著增加。此外，维达列汀本身能够在缺乏和存在葡萄糖的情况下动员胰岛细胞内的 Ca(2+)。从本研究中，我们得出以下结论：（A）维达列汀增加了糖尿病大鼠胰岛的血流；（B）胰岛胰岛素分泌独立于胰岛血流和 NO；（C）维达列汀抑制了糖尿病大鼠中过多的 NO 产生，这可防止由于过氧化物亚硝酸盐（ONOO(-)）离子的过度产生而对β细胞造成的损害，并防止细胞因子诱导的胰岛素释放抑制。
